tbuckley/cabot-search huggingface dataset:
Transferable exclusivity voucher: a flawed incentive to stimulate antibiotic innovation
Authors: Christine Årdal, Enrico Baraldi, Reinhard Busse, Rosa Castro, Francesco Ciabuschi, José Miguel Cisneros, Inge C Gyssens, Stephan Harbarth, Tomislav Kostyanev, Yohann Lacotte, Nicola Magrini, Anthony McDonnell, Annelie A Monnier, Suerie Moon, Elias Mossialos, Germán Peñalva, Marie-Cécile Ploy, Momir Radulović, Adrián Alonso Ruiz, John-Arne Røttingen, Michael Sharland, Evelina Tacconelli, Ursula Theuretzbacher, Sabine Vogler, Ute Wolff Sönksen, Kerstin Åkerfeldt, Otto Cars, Jim O'Neill
Journal: The Lancet (2023)
Association between Smoking Cessation and the Risk of Cholangiocarcinoma and Ampulla of Vater Cancer: A Nationwide Cohort Study
Authors: Joo-Hyun Park, Jung Yong Hong, Kyungdo Han
Journal: Liver Cancer (2023)

The association between smoking cessation and intrahepatic and extrahepatic cholangiocarcinoma (iCCA and eCCA) risk is unclear. Furthermore, the association in individuals with preexisting risk factors is unknown. We aimed to investigate the association between smoking status (especially smoking cessation) and CCA risk according to individuals' glycemic status.In this nationwide cohort study, 9,520,629 adults without cancer who underwent national health screening by the Korean National Health Insurance Service in 2009 were followed up through 2018. The hazard ratios (HRs) and 95% confidence intervals (CIs) for CCA were estimated after adjusting for potential confounders.During the 78.3 person-years of follow-up, 16,236 individuals were newly diagnosed with CCA. Quitters had a significantly lower risk of iCCA and eCCA compared to current smokers in all glycemic status groups (all p < 0.01). The HRs (95% CIs) for iCCA in current smokers and quitters were 1.33 (1.24-1.43) versus 0.98 (0.90-1.06) in individuals with normoglycemia, 1.49 (1.37-1.63) versus 1.17 (1.06-1.28) in individuals with prediabetes, and 2.15 (1.96-2.37) versus 1.58 (1.42-1.75) in individuals with diabetes, compared to never-smokers with normoglycemia. Current smokers with diabetes or prediabetes had a synergistically increased risk of iCCA (all p < 0.01). However, quitters with diabetes and prediabetes had an iCCA risk comparable to that of never-smokers. Analysis of eCCA yielded similar results. Smoking was not independently associated with the risk of the ampulla of Vater cancer. However, smoking combined with diabetes or prediabetes was associated with an increased risk of the ampulla of Vater cancer (all p < 0.05).Smoking cessation was associated with a reduced risk of CCA, despite the synergistically increased risk in current smokers with diabetes and prediabetes. Our findings suggest a crucial opportunity to reduce the risk of CCA. More individualized and intensive cancer prevention education is needed against CCA.
Insights into the accuracy of social scientists’ forecasts of societal change
Authors: Igor Grossmann, Amanda Rotella, Cendri A. Hutcherson, Konstantyn Sharpinskyi, Michael E. W. Varnum, Sebastian Achter, Mandeep K. Dhami, Xinqi Evie Guo, Mane Kara-Yakoubian, David R. Mandel, Louis Raes, Louis Tay, Aymeric Vie, Lisa Wagner, Matus Adamkovic, Arash Arami, Patrícia Arriaga, Kasun Bandara, Gabriel Baník, František Bartoš, Ernest Baskin, Christoph Bergmeir, Michał Białek, Caroline K. Børsting, Dillon T. Browne, Eugene M. Caruso, Rong Chen, Bin-Tzong Chie, William J. Chopik, Robert N. Collins, Chin Wen Cong, Lucian G. Conway, Matthew Davis, Martin V. Day, Nathan A. Dhaliwal, Justin D. Durham, Martyna Dziekan, Christian T. Elbaek, Eric Shuman, Marharyta Fabrykant, Mustafa Firat, Geoffrey T. Fong, Jeremy A. Frimer, Jonathan M. Gallegos, Simon B. Goldberg, Anton Gollwitzer, Julia Goyal, Lorenz Graf-Vlachy, Scott D. Gronlund, Sebastian Hafenbrädl, Andree Hartanto, Matthew J. Hirshberg, Matthew J. Hornsey, Piers D. L. Howe, Anoosha Izadi, Bastian Jaeger, Pavol Kačmár, Yeun Joon Kim, Ruslan Krenzler, Daniel G. Lannin, Hung-Wen Lin, Nigel Mantou Lou, Verity Y. Q. Lua, Aaron W. Lukaszewski, Albert L. Ly, Christopher R. Madan, Maximilian Maier, Nadyanna M. Majeed, David S. March, Abigail A. Marsh, Michal Misiak, Kristian Ove R. Myrseth, Jaime M. Napan, Jonathan Nicholas, Konstantinos Nikolopoulos, Jiaqing O, Tobias Otterbring, Mariola Paruzel-Czachura, Shiva Pauer, John Protzko, Quentin Raffaelli, Ivan Ropovik, Robert M. Ross, Yefim Roth, Espen Røysamb, Landon Schnabel, Astrid Schütz, Matthias Seifert, A. T. Sevincer, Garrick T. Sherman, Otto Simonsson, Ming-Chien Sung, Chung-Ching Tai, Thomas Talhelm, Bethany A. Teachman, Philip E. Tetlock, Dimitrios Thomakos, Dwight C. K. Tse, Oliver J. Twardus, Joshua M. Tybur, Lyle Ungar, Daan Vandermeulen, Leighton Vaughan Williams, Hrag A. Vosgerichian, Qi Wang, Ke Wang, Mark E. Whiting, Conny E. Wollbrant, Tao Yang, Kumar Yogeeswaran, Sangsuk Yoon, Ventura R. Alves, Jessica R. Andrews-Hanna, Paul A. Bloom, Anthony Boyles, Loo Charis, Mingyeong Choi, Sean Darling-Hammond, Z. E. Ferguson, Cheryl R. Kaiser, Simon T. Karg, Alberto López Ortega, Lori Mahoney, Melvin S. Marsh, Marcellin F. R. C. Martinie, Eli K. Michaels, Philip Millroth, Jeanean B. Naqvi, Weiting Ng, Robb B. Rutledge, Peter Slattery, Adam H. Smiley, Oliver Strijbis, Daniel Sznycer, Eli Tsukayama, Austin van Loon, Jan G. Voelkel, Margaux N. A. Wienk, Tom Wilkening
Journal: Nature Human Behaviour (2023)
Metabolism and epigenetics at the heart of T cell function
Authors: Leticia Soriano-Baguet, Dirk Brenner
Journal: Trends in Immunology (2023)

T cell subsets adapt and rewire their metabolism according to their functions and surrounding microenvironment. Whereas naive T cells rely on mitochondrial metabolic pathways characterized by low nutrient requirements, effector T cells induce kinetically faster pathways to generate the biomass and energy needed for proliferation and cytokine production. Recent findings support the concept that alterations in metabolism also affect the epigenetics of T cells. In this review we discuss the connections between T cell metabolism and epigenetic changes such as histone post-translational modifications (PTMs) and DNA methylation, as well as the 'extra-metabolic' roles of metabolic enzymes and molecules. These findings collectively point to a new group of potential therapeutic targets for the treatment of T cell-dependent autoimmune diseases and cancers.
Quantifying the effect of delaying the second COVID-19 vaccine dose in England: a mathematical modelling study
Authors: Natsuko Imai, Thomas Rawson, Edward S Knock, Raphael Sonabend, Yasin Elmaci, Pablo N Perez-Guzman, Lilith K Whittles, Divya Thekke Kanapram, Katy A M Gaythorpe, Wes Hinsley, Bimandra A Djaafara, Haowei Wang, Keith Fraser, Richard G FitzJohn, Alexandra B Hogan, Patrick Doohan, Azra C Ghani, Neil M Ferguson, Marc Baguelin, Anne Cori
Journal: The Lancet Public Health (2023)
Long-term evolution of comorbidities and their disease burden in individuals with and without HIV as they age: analysis of the prospective AGEhIV cohort study
Authors: Eveline Verheij, Anders Boyd, Ferdinand W Wit, Sebastiaan O Verboeket, Myrthe L Verburgh, Marc van der Valk, Maarten F Schim van der Loeff, Peter Reiss, P. Reiss, F.W.N.M. Wit, M. van der Valk, J. Schouten, K.W. Kooij, R.A. van Zoest, E. Verheij, S.O. Verboeket, B.C. Elsenga, M. Prins, M.F. Schim van der Loeff, L. del Grande, V. Olthof, I. Agard, S. Zaheri, M.M.J. Hillebregt, Y.M.C. Ruijs, D.P. Benschop, A. el Berkaoui, N.A. Kootstra, A.M. Harskamp-Holwerda, I. Maurer, M.M. Mangas Ruiz, A.F. Girigorie, B. Boeser-Nunnink, W. Zikkenheiner, S. Nolst Trenité, S.E. Geerlings, A. Goorhuis, J.W.R. Hovius, F.J.B. Nellen, T. van der Poll, J.M. Prins, W.J. Wiersinga, M. van Vugt, G. de Bree, J. van Eden, A.M.H. van Hes, F.J.J. Pijnappel, A. Weijsenfeld, S. Smalhout, M. van Duinen, A. Hazenberg, P.G. Postema, P.H.L.T. Bisschop, M.J.M. Serlie, P. Lips, E. Dekker, N. Dekker, J.M.R. Willemsen, L. Vogt
Journal: The Lancet HIV (2023)
Iron is a modifier of the phenotypes of <i>JAK2</i>-mutant myeloproliferative neoplasms
Authors: Jan Stetka, Marc Usart, Lucia Kubovcakova, Shivam Rai, Tata Nageswara Rao, Joshua Sutter, Hui Hao-Shen, Stefan Dirnhofer, Florian Geier, Michael Stephan Bader, Jakob R Passweg, Vania Manolova, Franz Dürrenberger, Nouraiz Ahmed, Timm Schroeder, Tomas Ganz, Elizabeta Nemeth, Laura Silvestri, Antonella Nai, Clara Camaschella, Radek C. Skoda
Journal: Blood (2023)

JAK2-V617F mutation causes myeloproliferative neoplasms (MPN) that can manifest as polycythemia vera (PV), essential thrombocythemia (ET) or primary myelofibrosis (PMF). PV patients at diagnosis already exhibited iron deficiency, whereas ET patients had normal iron stores. We examined the influence of iron availability on MPN phenotype in mice expressing JAK2-V617F and in mice expressing JAK2 with a N542-E543del mutation in exon 12 (E12). At baseline on control diet, all JAK2-mutant mouse models with PV-like phenotype displayed iron deficiency, although E12 mice maintained more iron for augmented erythropoiesis than JAK2-V617F mutant mice. In contrast, JAK2-V617F mutant mice with an ET-like phenotype had normal iron stores comparable to wildtype (WT) mice. On low-iron diet, JAK2-mutant mice and WT controls increased platelet production at the expense of erythrocytes. Mice with PV phenotype responded to parenteral iron injections by decreasing platelet counts and further increasing hemoglobin and hematocrit, whereas no changes were observed in WT controls. Alterations of iron availability primarily affected the pre-megakaryocyte erythrocyte progenitors (pre-MegE), which constitute the iron-responsive stage of hematopoiesis in JAK2-mutant mice. The orally administered ferroportin inhibitor vamifeport and the minihepcidin PR73 normalized hematocrit and hemoglobin levels in JAK2-V617F and E12 mutant mouse models of PV, suggesting that ferroportin inhibitors and minihepcidins could be used in the treatment of PV patients.
How I Treat AML in 2023 Incorporating the Updated Classifications and Guidelines
Authors: Firas El Chaer, Christopher S Hourigan, Amer M. Zeidan
Journal: Blood (2023)

The European LeukemiaNet (ELN) recently revised both the clinical (2022) and measurable residual disease (MRD) testing (2021) guidelines for acute myeloid leukemia (AML). Updated World Health Organization (WHO) and an International Consensus Classification (ICC) for myeloid neoplasms were also published in 2022. Together, these documents update the classification, risk stratification, prognostication, monitoring recommendations, and response assessment for patients with AML. Increased appreciation of the genetic drivers of AML over the past decade and our increasingly sophisticated understanding of AML biology have been translated into novel therapies and more complex clinical treatment guidelines. Somatic genetic abnormalities and germline predispositions now define and guide treatment and counseling for subtypes of this hematologic malignancy. In this paper, we discuss how we approach AML in daily clinical practice taking into consideration these recent updates in the context of new treatments and discoveries over the past decade.
Unusual Adverse Events in a Patient With BRAF-Mutated Non–Small Cell Lung Cancer Treated With BRAF/MEK Inhibition
Authors: Rohan Maniar, Stephanie M. Gallitano, Sameera Husain, Golnaz Moazami, Michael J. Weiss, Catherine A. Shu
Journal: Journal of the National Comprehensive Cancer Network (2023)

BRAF/MEK inhibition remains standard of care for treatment of BRAF-mutated non-small cell lung cancer (NSCLC). Although common adverse events (AEs) have been reported through clinical trials and ongoing clinical practice, only a handful of reports have detailed unusual adverse events associated with these medications. This report presents a patient with BRAF-mutated NSCLC treated with dabrafenib and trametinib who experienced 2 unusual AEs-Sweet syndrome and MEK-associated retinopathy-that responded to steroid treatment. The patient was able to continue BRAF/MEK inhibition through a coordinated multidisciplinary approach. This case highlights the importance for all clinicians to recognize unusual AEs associated with BRAF/MEK inhibition, particularly in the setting of expanded use for all BRAF V600E-mutated solid tumors.
Translational molecular imaging and drug development in Parkinson’s disease
Authors: Ahmed Haider, Nehal H. Elghazawy, Alyaa Dawoud, Catherine Gebhard, Thomas Wichmann, Wolfgang Sippl, Marius Hoener, Ernest Arenas, Steven H. Liang
Journal: Molecular Neurodegeneration (2023)

Abstract Parkinson’s disease (PD) is a progressive neurodegenerative disorder that primarily affects elderly people and constitutes a major source of disability worldwide. Notably, the neuropathological hallmarks of PD include nigrostriatal loss and the formation of intracellular inclusion bodies containing misfolded α-synuclein protein aggregates. Cardinal motor symptoms, which include tremor, rigidity and bradykinesia, can effectively be managed with dopaminergic therapy for years following symptom onset. Nonetheless, patients ultimately develop symptoms that no longer fully respond to dopaminergic treatment. Attempts to discover disease-modifying agents have increasingly been supported by translational molecular imaging concepts, targeting the most prominent pathological hallmark of PD, α-synuclein accumulation, as well as other molecular pathways that contribute to the pathophysiology of PD. Indeed, molecular imaging modalities such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) can be leveraged to study parkinsonism not only in animal models but also in living patients. For instance, mitochondrial dysfunction can be assessed with probes that target the mitochondrial complex I (MC-I), while nigrostriatal degeneration is typically evaluated with probes designed to non-invasively quantify dopaminergic nerve loss. In addition to dopaminergic imaging, serotonin transporter and N- methyl-D-aspartate (NMDA) receptor probes are increasingly used as research tools to better understand the complexity of neurotransmitter dysregulation in PD. Non-invasive quantification of neuroinflammatory processes is mainly conducted by targeting the translocator protein 18 kDa (TSPO) on activated microglia using established imaging agents. Despite the overwhelming involvement of the brain and brainstem, the pathophysiology of PD is not restricted to the central nervous system (CNS). In fact, PD also affects various peripheral organs such as the heart and gastrointestinal tract – primarily via autonomic dysfunction. As such, research into peripheral biomarkers has taken advantage of cardiac autonomic denervation in PD, allowing the differential diagnosis between PD and multiple system atrophy with probes that visualize sympathetic nerve terminals in the myocardium. Further, α-synuclein has recently gained attention as a potential peripheral biomarker in PD. This review discusses breakthrough discoveries that have led to the contemporary molecular concepts of PD pathophysiology and how they can be harnessed to develop effective imaging probes and therapeutic agents. Further, we will shed light on potential future trends, thereby focusing on potential novel diagnostic tracers and disease-modifying therapeutic interventions.
No-touch endoscopic full-thickness resection technique for gastric gastrointestinal stromal tumors
Authors: Tao Chen, Yun-Wei Zhang, Jing-Jing Lian, Hai-Bin Zhang, Ai-Ping Xu, Fang Li, Xiao-Han Yan, Ben-Song Duan, Zi-Ying Zhao, Yuan Chu, Li Shen, Jia Cao, Li Zhang, Liang Zheng, Shu-Guang Chu, Mei-Dong Xu
Journal: Endoscopy (2023)

Background There remain concerns regarding the technical feasibility of endoscopic resection for large gastrointestinal stromal tumors (GISTs), mainly relating to the risk of tumor rupture and the adequacy of the resection margins. This study aimed to evaluate the feasibility and therapeutic outcomes of the newly developed no-touch endoscopic full-thickness resection (NT-EFTR) technique for GISTs. Methods In this retrospective study, 92 patients with gastric GISTs undergoing NT-EFTR were included. Clinicopathological, endoscopic, and follow-up data were collected and analyzed. Results The median tumor size was 2.5 cm and en bloc resection was achieved in all patients with negative surgical margins. The median time of the NT-EFTR procedure was 59.5 minutes. Large tumors (&gt; 3.0 cm), extraluminal tumor growth pattern, and large gastric defects were significant contributors to long operative times. Patients were discharged within 4 days postoperatively. During follow-up, all patients were free from local recurrence and distant metastasis. Conclusions NT-EFTR was a feasible method for the resection of gastric GISTs and can be expected to achieve complete radical resection. Large tumors with extraluminal growth and large gastric defects impact procedural difficulty.
Modified technique for deployment of a lumen-apposing metal stent during endoscopic ultrasound-guided choledochoduodenostomy in minimally dilated duct
Authors: Jimil Shah, Anuraag Jena, Vaneet Jearth, Anupam K. Singh
Journal: Endoscopy (2023)

Electrocautery-enhanced lumen-apposing metal stent (EC-LAMS) has been routinely used for endoscopic ultrasound (EUS)-guided choledochoduodenostomy (CDS) with high technical and clinical success [1]. One of the major factors that determines technical success is common bile duct (CBD) diameter. CBD size < 15 mm is associated with a high risk of technical failure and maldeployment of the distal flange [2] [3]. Correct deployment of the distal flange inside the CBD is one of the most crucial steps of the procedure and, in cases of a marginally dilated duct, there is little space for opening of the distal flange, which increases the risk of maldeployment.
Successful omental patch for huge colonic perforation using regraspable clip
Authors: Kohei Ono, Ken Ohata, Nao Takeuchi, Shunya Takayanagi, Yoshiaki Kimoto, Ryoju Negishi, Yohei Minato
Journal: Endoscopy (2023)

A 79-year-old woman with a 20-mm early-stage colorectal cancer of the ascending colon underwent endoscopic submucosal dissection (ESD). A novel complete closure using a regraspable clip (Sureclip; Micro-Tech Co., Ltd, Nanjing, China) ([Fig. 1]) was applied for a large perforation that occurred during procedure.
Spigelman IV: can intensive cold snaring avoid duodenectomy in familial adenomatous polyposis?
Authors: James E. East
Journal: Endoscopy (2023)

Upper gastrointestinal surveillance is recommended for patients with familial adenomatous polyposis (FAP) who develop multiple duodenal adenomas as well as colonic adenomas. It is more than three decades since the St. Mark’s Hospital group, London published a scoring system for duodenal polyposis in FAP, the “Spigelman classification” [1]. The classification groups patients into stages from 0 to IV based on the number, size, and pathology (villosity and grade of dysplasia) of polyps, including biopsies from the duodenal ampulla and peri-ampullary area. The relevance of this system for assessing risk was demonstrated in a subsequent study where the risk over a 10-year period of duodenal cancer was only 2 %–3 % in patients with initial scores II and III, but reached 36 % at stage IV [2].
Spatial and molecular profiling of the mononuclear phagocyte network in Classic Hodgkin lymphoma
Authors: Benjamin J Stewart, Martin Fergie, Matthew Young, Claire Jones, Ashwin Sachdeva, Alex E Blain, Chris M Bacon, Vikki Rand, John R Ferdinand, Kylie Renee James, Krishnaa T Mahbubani, Catherine Elizabeth Hook, Nico Jonas, Nicholas Coleman, Kourosh Saeb-Parsy, Matthew Collin, Menna Clatworthy, Sam Behjati, Christopher D Carey
Journal: Blood (2023)
Management of Residual Nonretroperitoneal Disease in Postchemotherapy Nonseminomatous Germ-Cell Tumors
Authors: Jennifer M. King, Michael Cheng, Kenneth Kesler, Ryan Ashkar, Sandra K. Althouse, Nasser H. Hanna, Lawrence H. Einhorn, Nabil Adra
Journal: Journal of Clinical Oncology (2023)

The majority of patients with advanced nonseminomatous germ-cell tumor are cured with combination chemotherapy and surgical resection of residual disease when appropriate. In patients with both retroperitoneal (RP) and non-RP postchemotherapy residual disease, management of the non-RP disease is typically guided by pathologic findings at the time of RP resection. There are limited data to help guide management decisions in patients with non-RP postchemotherapy residual disease alone.The prospectively maintained Indiana University testicular cancer database was queried for patients with metastatic nonseminomatous germ-cell tumor treated between 1990 and 2021 who had residual non-RP disease in the absence of residual RP disease after completing either first-line or salvage chemotherapy.One hundred twenty-nine patients met eligibility and were included in this analysis. Seventy-five patients had teratoma in the primary tumor site, while 54 did not. Of those with teratoma in the primary, 55% had at least one postchemotherapy non-RP surgical specimen with teratomatous elements compared with 17% of those without teratoma in the primary (P < .001). Of those without teratoma in the primary site, 56% had at least one postchemotherapy non-RP surgical specimen with active germ-cell tumor compared with 31% of those with teratoma in the primary (P = .0046).The presence of teratoma in the primary tumor site is associated with a higher rate of teratoma in postchemotherapy residual non-RP disease. Patients without teratoma in the primary tumor should still be considered for resection of residual postchemotherapy disease that could harbor teratoma or active germ-cell tumor.
Plasma Micro-RNA 371 Expression in Early-Stage Germ Cell Tumors: Are We Ready to Move Toward Biology-Based Decision Making?
Authors: Muhannad Alsyouf, Lucia Nappi, Craig Nichols, Siamak Daneshmand
Journal: Journal of Clinical Oncology (2023)

Testicular germ cell tumors (GCTs) are the most common malignancy in young men with an increasing prevalence. 1 Approximately 90% of all GCTs present with clinical stage (CS)-I (confined to the resected testis) or CS-II (regionally confined) disease, with only 10% presenting with dissemination above the diaphragm or involving visceral organs. 1 In patients with CS-I disease, active surveillance is, by far, the dominant management strategy in the United States and is strongly endorsed in North American guidelines. 2 In CS-II disease, retroperitoneal lymph node dissection (RPLND), chemotherapy, or regional radiation (in seminoma) are standard management strategies.Overall, the current treatment options for CS I-IIA/B disease are excellent with cure rates of 95%-100%.
Endoscopic resection of a huge Vanek’s tumor (inflammatory fibroid polyp)
Authors: Xue Peng, Jianjun Li, Qiujian Qiao, Xinwei Diao, Muhan Lü, Jianying Bai, Chaoqiang Fan
Journal: Endoscopy (2023)

A 43-year-old man vomited a "sausage-like" mass into the mouth after drinking a bottle of beer; the mass was then re-swallowed. He subsequently experienced intermittent retrosternal discomfort. Esophagogastroduodenoscopy (EGD) at the local hospital showed a huge esophageal tumor. The patient was transferred to our hospital for further endoscopic resection.